Neighboring groups, powerful

Since the phenoxyls possess an S = ground state, they have been carefully studied by electron paramagnetic spectroscopy (EPR) and related techniques such as electron nuclear double resonance (ENDOR), and electron spin-echo envelope modulation (ESEEM). These powerful and very sensitive techniques are ideally suited to study the occurrence of tyrosyl radicals in a protein matrix (1, 27-30). Careful analysis of the experimental data (hyperfine coupling constants) provides experimental spin densities at a high level of precision and, in addition, the positions of these tyrosyls relative to other neighboring groups in the protein matrix. 

In making its nucleophilic attack, a neighboring group competes with outside molecules that are often intrinsically much stronger nucleophiles. Yet the evidence clearly shows that the neighboring group enjoys—for its nucleophilic power—a tremendous advantage over these outside nucleophiles. Why is this The answer is quite simple because it is there. 

The NOE spectra. The irradiation with monochromatic r.f. of the same frequency as the resonance frequency of one of the groups (but of lower power than that required for the decoupling experiment), produces an increasing intensity for the signals of the through-space neighboring groups. 

They also described the reaction of the diacetate (272) with base, to give (273), a reaction that emphasizes the powerful neighboring-group abihty of the thioalkoxide ion to eject acetate ion, a poor leaving-group. The conversion of the epoxide (268) into the episulfide (267) by thiourea was also reported.As was pointed out by Bordwell and Andersen, the... 

In some cases, nucleophilic attack by solvent may be an undesired reaction pathway, but a protic solvent of high ionizing power may be required to provide adequate heterolytic reactivity or electrophilic catalysis. Examples include many cyclizations and reactions involving neighboring group participation (fcA processes) (28, 29). Suitable solvents include TFE (30-37), HFIP (35-38), aqueous sulfuric acid (39), and carboxylic acids (28, 29). 

Sulfur atoms are often powerful nucleophiles, and the participation of sulfur as a neighboring group is common. Figure 21.11 shows an example of the third kind of clue, a reaction in which there is an unexpectedly rapid rate. Both hexyl chloride... 

Proponents of neighboring group partidpation asserted that these pieces of stereochemical data constituted powerful eddence for a delocalized ion. First of all, it is only the exo tosylate that can form such an ion directly, and the exo compound did indeed react at a greater rate than the endo isomer (Fig. 21.52). 

As exemplified with the synthesis of 105 (Scheme 1.2), the latter compounds are obtained via the displacement a-chloroalkylboronates with the hexamethyldisilazide anion. This example also emphasizes the powerful neighboring group effect of boron, which allows selectivity in the addition of Cl2CHLi in the presence of a primary alkyl bromide [323]. Other applications of (a-haloalkyl)boronates in stereoselective synthesis are detailed in Chapter 8. 

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